Role of LRRK2 in physiological activities, diseases, and therapy

ABSTRACT: Leucine-rich repeat kinase 2 (LRRK2) is a critical target for the treatment of Parkinson's disease (PD) and potentially other diseases. LRRK2 is involved in intracellular signaling, immune response, and inflammation, with key roles in both the central nervous system and peripheral tissues. LRRK2 mutations are linked to cellular dysfunction including mitochondrial and neuronal damage and can disrupt signaling pathway balance, thereby contributing to PD and other disorders. Inhibiting LRRK2 kinase activity shows potential for treating PD by correcting cellular imbalances and reducing neuronal damage. However, risks associated with regulating a multifunctional protein must be addressed. Further research on the molecular partners and tissue-specific functions of LRRK2 is essential for developing targeted therapies and improving treatment options for related diseases. This review offers a comprehensive analysis of LRRK2, with a focus on its physiological functions, disease involvement, and emerging therapeutic strategies.